Safety and Immune Response to a Prime-Boost Vaccination Schedule in HIV-infected Patients

NCT00270465 | Completed Phase 1

• 2 other identifiers: 06005606-I-0056
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Study Design: This is a Phase I, randomized, placebo-controlled, double-blinded study to examine safety, tolerability and immune response of a prime-boost vaccination regimen for treatment of HIV infection. The vaccination schedule consists of three injections of a multiclade HIV plasmid DNA vaccine followed by one injection of a multiclade recombinant adenoviral vector vaccine (rAd), in HIV-infected adults. The hypothesis is that this vaccination regimen will be safe and elicit an immune response in HIV-infected subjects. The primary objectives are related to evaluating the safety and tolerability of the vaccination regimen and assessing the effect of vaccination on humoral and cellular immune responses to vaccine-specific HIV antigens. Product Description: VRC-HIVDNA016-00-VP is composed of 6 closed, circular DNA plasmids that are each 16.67% (by weight) of the vaccine. Each of the 6 plasmids in this vaccine expresses a single gene product. Plasmids VRC 4401, VRC 4409 and VRC 4404 are designed to express clade B HIV-1 Gag, Pol and Nef, respectively. VRC 5736, VRC 5737, and VRC 5738 are designed to express HIV-1 Env glycoprotein from clade A, clade B, and clade C, respectively. Each DNA vaccination will be 1 mL of vaccine administered intramuscularly (IM) using the Biojector 2000 Needle-Free Injection Management System. Phosphate buffered saline (PBS) will be used as the placebo for the DNA vaccine. VRC-HIVADV014-00-VP (rAd) is a recombinant product composed of 4 adenoviral vectors (Ad) (in a 3:1:1:1 ratio) that encode the HIV-1 Gag/Pol polyprotein from clade B and HIV-1 Env glycoproteins from clades A, B, and C, respectively. Injections of 10(10) PU will be administered IM by needle and syringe. The final formulation buffer (FFB) will be used as the placebo for the rAd vaccine. Subjects: HIV-infected adult volunteers (18-50 years old) on stable highly active antiretroviral therapy (HAART) therapy who have a CD4+ cell count greater than 350 cells/mm3 and have had a viral load (VL) less than 400 copies/mL for at least six months and a viral load of less than 50 copies/mL within 4 weeks prior to enrollment. Study Plan: Fifteen volunteers will be enrolled and randomized in a 2:1 ratio to vaccine:control (10 DNA prime with rAd boost:5 PBS with FFB placebo). A Data and Safety Monitoring Board (DSMB) will review the study every 6 months. Subjects will be evaluated for safety and immunogenicity for 48 weeks, which is 24 weeks after the target date for the booster vaccination. Study Duration: Subjects will be followed for 48 weeks after enrollment into the study.

Conditions

HIV

Keywords

HIV-positive; Treatment Interruption; Therapeutic Vaccine; HIV/AIDS; Virologic Response; HIV Positive

Interventions

VRC-HIVDNA016-00-VP DRUG

VRC-HIVADV014-00-VP DRUG

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A participant must meet all of the following criteria:
• HIV-1 infection defined as documented by any approved ELISA test kit and confirmed with a Western blot at any time prior to study entry.
• On stable highly active antiretroviral therapy (HAART), as defined by the Department of Health and Human Services (http://www.aidsinfo.nih.gov/other/cbrochure/english/04\_en.pdf), with no change in the drugs included in the treatment regimen for a minimum of 8 weeks prior to enrollment.
• CD4+ cell count greater than 350 cells/mm(3) at 2 different time points that meet the following criteria: The first result must be from between 4 weeks to 36 weeks prior to enrollment obtained at any laboratory used by a health care facility. The second result must be obtained at the NIH Clinical Center within 28 days prior to enrollment. There must be at least 28 days between the two tests used for eligibility.
• HIV-1 RNA viral load (VL) consistently less than 400 copies/mL for six months or longer prior to enrollment (as reported by the subject). Documentation must include the following: at least one documented HIV RNA PCR result showing VL less than 400 copies/mL obtained between 12-36 weeks prior to enrollment at any laboratory used by a health care facility and another VL less than 50 copies/mL that must be obtained at the NIH Clinical Center within 28 days prior to study entry.
• Men and women aged 18-50 years.
• Ability and willingness of subject to give written informed consent.
• Laboratory Criteria within 28 days prior to enrollment:
• Absolute neutrophil count (ANC) greater than or equal to 750/mm(3).
• Hemoglobin greater than or equal to 9.0 g/dL.
• Platelet count greater than or equal to 100,000/mm(3).
• Creatinine less than or equal to 1.5 x upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x ULN.
• Total bilirubin less than or equal to 2.5 x ULN; a higher total bilirubin value may be permitted if the subject is taking atanazir (ATV) or indinavir (IDV) and the elevation in total bilirubin is due to increased indirect (unconjugated) bilirubin.
• Serum lipase less than or equal to 2.0 x ULN.

You may not qualify if:

• Women:
• Breast-feeding or planning to become pregnant during the 48 weeks of study participation.
• A volunteer will be excluded if he/she has a medication history of one or more of the following:
• Receipt of live attenuated vaccines or investigational research agents within 30 days prior to study entry.
• Receipt of blood products within 120 days prior to study entry.
• Receipt of immunoglobulin within 60 days prior to study entry.
• Receipt of medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal, or allergy treatment with antigen injections) within 14 days prior to study entry.
• Receipt of experimental HIV vaccines in the preceding 2 years. Individuals that received a placebo in a prior HIV vaccine trial are not excluded.
• Receipt of immunosuppressive medications within the past 6 months (e.g., oral/parenteral/inhaled corticosteroids, and/or cytotoxic medications). NOTE: The following will be allowed: corticosteroid nasal spray for allergic rhinitis; topical corticosteroids for acute, uncomplicated dermatitis; over the counter medications for acute, uncomplicated dermatitis for a period not longer than 14 days; short-acting beta-agonists in controlled asthmatics; or a short course (10 days or less) of corticosteroids for a non-chronic condition at least 2 weeks prior to enrollment in the study.
• Receipt of IL-2 within the preceding 1 year.
• A volunteer with any of the following conditions will be excluded:
• Positive hepatitis B virus (HBV) surface antigen or positive hepatitis C virus (HCV) antibody or detectable HCV viral load.
• History of CD4+ counts less than 100 cells/mm(3) on two or more occasions in the past.
• History of serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. Subjects who have a history of an adverse reaction to pertussis vaccine as a child may enroll.
• History of autoimmune disease; immunodeficiency (other than HIV infection); asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the prior 2 years or that requires the use of oral or intravenous corticosteroids; diabetes (Type I or II with the exception of gestational diabetes); thyroidectomy or history of thyroid disease in the past 12 months; or serious angioedema episodes within the previous 3 years or requiring medication in the previous 2 years.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Calmy A, Pascual F, Ford N. HIV drug resistance. N Engl J Med. 2004 Jun 24;350(26):2720-1. doi: 10.1056/NEJM200406243502621. No abstract available.

  PMID: 15215494 BACKGROUND

• Clough LA, D'Agata E, Raffanti S, Haas DW. Factors that predict incomplete virological response to protease inhibitor-based antiretroviral therapy. Clin Infect Dis. 1999 Jul;29(1):75-81; discussion 82-4. doi: 10.1086/520185.

  PMID: 10433568 BACKGROUND

• Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions. Ann Intern Med. 1999 Jul 20;131(2):81-7. doi: 10.7326/0003-4819-131-2-199907200-00002.

  PMID: 10419445 BACKGROUND

• Casazza JP, Bowman KA, Adzaku S, Smith EC, Enama ME, Bailer RT, Price DA, Gostick E, Gordon IJ, Ambrozak DR, Nason MC, Roederer M, Andrews CA, Maldarelli FM, Wiegand A, Kearney MF, Persaud D, Ziemniak C, Gottardo R, Ledgerwood JE, Graham BS, Koup RA; VRC 101 Study Team. Therapeutic vaccination expands and improves the function of the HIV-specific memory T-cell repertoire. J Infect Dis. 2013 Jun 15;207(12):1829-40. doi: 10.1093/infdis/jit098. Epub 2013 Mar 12.

  PMID: 23482645 DERIVED

MeSH Terms

Conditions

HIV Seropositivity; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: December 24, 2005
• First Posted: December 26, 2005
• Study Start: December 21, 2005
• Primary Completion: June 25, 2009
• Study Completion: June 25, 2009
• Last Updated: July 2, 2017

Record last verified: 2009-06-25

Locations

US (1)